Pirkle-type CSPs chiral recognition mechanisms

Different classifications for the chiral CSPs have been described. They are based on the chemical structure of the chiral selectors and on the chiral recognition mechanism involved. In this chapter we will use a classification based mainly on the chemical structure of the selectors. The selectors are classified in three groups (i) CSPs with low-molecular-weight selectors, such as Pirkle type CSPs, ionic and ligand exchange CSPs, (ii) CSPs with macrocyclic selectors, such as CDs, crown-ethers and macrocyclic antibiotics, and (iii) CSPs with macromolecular selectors, such as polysaccharides, synthetic polymers, molecular imprinted polymers and proteins. These different types of CSPs, frequently used for the analysis of chiral pharmaceuticals, are discussed in more detail later. 

Most chiral HPLC analyses are performed on CSPs. General classification of CSPs and rules for which columns may be most appropriate for a given separation, based on solute structure, have been described in detail elsewhere. Nominally, CSPs fall into four primary categories (there are additional lesser used approaches) donor-acceptor (Pirkle) type, polymer-based carbohydrates, inclusion complexation type, and protein based. Examples of each CSP type, along with the proposed chiral recognition mechanism, analyte requirement(s), and mode of operation, are given in Table 3. Normal-phase operation indicates that solute elution is promoted by the addition of polar solvent, whereas in reversed-phase operation elution is promoted by a decrease in mobile-phase polarity. 

As discussed in Sect. 3.5, the interactions involved in the chiral recognition on Pirkle-type CSPs are mainly attractive forces, such as k-jt, hydrogen-bonding, and dipole-dipole interactions. Although bonded Pirkle-type CSPs have been used in reversed phase and polar nonaqueous mobile phase, most of the applications were found in normal-phase mode. With the introduction of SFC for the resolution of enantiomers [185], bonded Pirkle-type CSPs were among the most studied CSPs in the early application of chiral SFC [172, 175, 181, 186], Comparable enantioselectivity and the same elution order of enantiomers were usually observed for the enantioseparations of many compounds. Accordingly, similar chiral recognition mechanisms were believed to operate in both LC and SFC conditions [186]. However, when the enantioseparations of jt-acidic compounds on the n-acidic... 

An understanding of the recognition of chirality at a molecular level has become of interest in many fields of chemistry and biology. In the past decade, many attempts to clarify the mechanism of chiral recognition on CSPs for liquid chromatography have been made by means of chromatography, NMR spectroscopy,199 202 X-ray analysis, and computational methods.203 - 206 The successful studies have been mostly carried out for the small-molecule CSPs, especially cyclodextrin-based CSPs and Pirkle-type (brush-type) CSPs. In contrast, only a few mechanistic studies on chiral discrimination at the molecular... 

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